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Coevolution at the proteome scale

Rosetta@home - Po, 15.07.2019 - 21:23

Last week, a report was published in Science describing the identification of hundreds of previously uncharacterized protein–protein interactions in E. coli and the pathogenic bacterium M. tuberculosis. These include both previously unknown protein complexes and previously uncharacterized components of known complexes. This research was led by postdoctoral fellow Qian Cong and included former Baker lab graduate student Sergey Ovchinnikov, now a John Harvard Distinguished Science Fellow at Harvard. Rosetta@home was used for much of the computing required for this work. Congratulations and thank you to all R@h volunteers.

For more information about this work click here.
Kategórie: Novinky z projektov

Protein arrays on mineral surfaces

Rosetta@home - Po, 15.07.2019 - 21:12

Last week, the Baker Lab in collaboration with the De Yoreo lab at PNNL published a report in Nature describing the design of synthetic protein arrays that assemble on the surface of mica, a common and exceptionally smooth crystalline mineral. This work provides a foundation for understanding how protein-crystal interactions can be systematically programmed. Although R@h was not directly used for this research, previously designed subunits were validated using R@h. Congratulations to all R@h volunteers and thank you for your continued contributions.

For more details click here.
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50th Anniversary of the Moon Landing Challenge starts July 15th 20:17 UTC

PrimeGrid - Po, 15.07.2019 - 12:42
"Thirty seconds and counting. Astronauts report it feels good. T-25 seconds. Twenty seconds and counting. T-15 seconds, guidance is internal. 12, 11, 10, 9 ... ignition sequence start ... 6, 5, 4, 3, 2, 1, 0 ... All engines running. Liftoff! We have a liftoff ... 32 minutes past the hour, liftoff on Apollo 11!" To celebrate the 50th Anniversary of humans landing on the Moon, PrimeGrid is running a 5 day challenge from July 15th 2019, 20:17 UTC until July 20th, 20:17 UTC. Work units from the PPS (LLR) project, which are downloaded and completed during the challenge will count towards your challenge score. Many primes are expected to be found. For more information and discussion, please see the official challenge thread:
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Science non-stop: another paper, another badge

GPUGRID - So, 13.07.2019 - 10:36
...and here's another badge for another publication issued in 2018, Dopamine D3 receptor antagonist reveals a cryptic pocket in aminergic GPCRs. This one is also on Sci. Rep., open access. Here, the authors used Gpugrid-based simulations to reconcile experimental results on Dopamine D3 receptor antagonists with their molecular structures. They used the large-scale high-throughput molecular dynamics with Markov state models (MSMs) to determine an alternative and possibly elusive pose ("cryptic") consistent with the mutation data. Thanks to every contributor! Noelia Ferruz, Stefan Doerr, Michelle A. Vanase-Frawley, Yaozhong Zou, Xiaomin Chen, Eric S. Marr, Robin T. Nelson, Bethany L. Kormos, Travis T. Wager, Xinjun Hou, Anabella Villalobos, Simone Sciabola & Gianni De Fabritiis Dopamine D3 receptor antagonist reveals a cryptic pocket in aminergic GPCRs Scientific Reportsvolume 8, Article number: 897 (2018) The recent increase in the number of X-ray crystal structures of G-protein coupled receptors (GPCRs) has been enabling for structure-based drug design (SBDD) efforts. These structures have revealed that GPCRs are highly dynamic macromolecules whose function is dependent on their intrinsic flexibility. Unfortunately, the use of static structures to understand ligand binding can potentially be misleading, especially in systems with an inherently high degree of conformational flexibility. Here, we show that docking a set of dopamine D3 receptor compounds into the existing eticlopride-bound dopamine D3 receptor (D3R) X-ray crystal structure resulted in poses that were not consistent with results obtained from site-directed mutagenesis experiments. We overcame the limitations of static docking by using large-scale high-throughput molecular dynamics (MD) simulations and Markov state models (MSMs) to determine an alternative pose consistent with the mutation data. The new pose maintains critical interactions observed in the D3R/eticlopride X-ray crystal structure and suggests that a cryptic pocket forms due to the shift of a highly conserved residue, F6.52. Our study highlights the importance of GPCR dynamics to understand ligand binding and provides new opportunities for drug discovery.
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M Queens for arm64

yoyo@home - Pi, 12.07.2019 - 00:00
We released now also a M Queens app for arm64.
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More Nbody Runs on MilkyWay@home

Milkyway@Home - St, 10.07.2019 - 21:04
Hey all,

I've put up some more nbody runs for MilkyWay@home. Here are the names of the new runs:
If you find any problems with these runs, please do not hesitate to contact us. Thank you all for your continued support!

Kategórie: Novinky z projektov

OpenZika Nears End of Work on World Community Grid

World Community Grid - Ut, 09.07.2019 - 21:10
The OpenZika researchers are making ambitious plans to analyze the data that has been processed by World Community Grid volunteers over the past three years. Learn about the next steps for the project in this comprehensive update.
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New badge, new(ish) paper

GPUGRID - Ut, 09.07.2019 - 12:08
Dears, we added a badge for a (not-so-recent-any-more) paper Dynamic and Kinetic Elements of µ-Opioid Receptor Functional Selectivity. The abstract is here and the text is open-access. It is interesting because it provides evidence about the kinetics (i.e., transient conformational changes) incurred by the µ-opioid receptor (MOR) upon binding to drugs. MOR is part of the large and important GPCR protein family, which is targeted by approx ~30% of the current drugs. Abhijeet Kapoor, Gerard Martinez-Rosell, Davide Provasi, Gianni de Fabritiis & Marta Filizola Dynamic and Kinetic Elements of µ-Opioid Receptor Functional Selectivity Scientific Reports volume 7, Article number: 11255 (2017) While the therapeutic effect of opioids analgesics is mainly attributed to µ-opioid receptor (MOR) activation leading to G protein signaling, their side effects have mostly been linked to β-arrestin signaling. To shed light on the dynamic and kinetic elements underlying MOR functional selectivity, we carried out close to half millisecond high-throughput molecular dynamics simulations of MOR bound to a classical opioid drug (morphine) or a potent G protein-biased agonist (TRV-130). Statistical analyses of Markov state models built using this large simulation dataset combined with information theory enabled, for the first time: a) Identification of four distinct metastable regions along the activation pathway, b) Kinetic evidence of a different dynamic behavior of the receptor bound to a classical or G protein-biased opioid agonist, c) Identification of kinetically distinct conformational states to be used for the rational design of functionally selective ligands that may eventually be developed into improved drugs; d) Characterization of multiple activation/deactivation pathways of MOR, and e) Suggestion from calculated transition timescales that MOR conformational changes are not the rate-limiting step in receptor activation.
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M Queens M=27 started

yoyo@home - Ut, 09.07.2019 - 00:00
The 27x27 board is the highest-order board that has been completely enumerated. In 2016, after more than a year of computation on FPGA, 29,363,495,934,315,694 solutions were enumerated at University of Dresden. We want ot verify this number and have to run 2.2 million workunits, which we compute twice. On the progress bar you see 25% of it. We'll see if we need also a year for this.
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GFN-524288 Mega Prime!

PrimeGrid - Po, 08.07.2019 - 14:20
On 29 June 2019, 00:54:18 UTC, PrimeGrid’s Generalized Fermat Prime Search found the Generalized Fermat mega prime: 2877652^524288+1 The prime is 3,386,397 digits long and enters Chris Caldwell's The Largest Known Primes Database ranked 3rd for Generalized Fermat primes and 26th overall. The discovery was made by Roman Vogt (Tabaluga) of Germany using an NVIDIA GeForce GTX 1060 in an Intel(R) Core(TM) i7-2700K CPU @ 3.50GHz CPU with 16GB RAM, running Windows 10. This GPU took about 1 hour and 42 minutes to probable prime (PRP) test with GeneferOCL5. Roman is a member of the Sicituradastra. team. The PRP was verified on 29 June 2019, 08:52:47 by Carlo Villa (carlo) using an NVIDIA GeForce 830M in an Intel(R) Core(TM) i5-5200U CPU @ 2.20GHz with 8GB RAM, running Windows 10. This GPU took about 16 hours and 55 minutes to probable prime (PRP) test with GeneferOCL5. The PRP was confirmed prime by an Intel(R) Xeon(R) CPU E3-1240 v6 @ 3.70GHz with 4GB RAM, running Linux. This computer took about 25 hours 53 minutes to complete the primality test using multithreaded LLR. For more details, please see the official announcement.
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New SETI Perspectives: "Seeing the Unseeable: The Black Hole Image"

SETI@Home - Pi, 05.07.2019 - 23:10
Richard Lawn has posted another interesting article to "SETI Perspectives". This one is titled Seeing the Unseeable: The Black Hole Image and is about the Event Horizon Telescope's image of the black hole in M87.
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M Queens for M=27

yoyo@home - Pi, 05.07.2019 - 00:00
With our last run for M=24 we verified the Windows app and the validation against Linux. With our test runs we were able to confirm the amount of solutions for M=21 and M=24. So now we are ready for M=27. Some workunits are already created.
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Thanks for supporting SixTrack at LHC@Home and updates

LHC@home - Ut, 23.01.2018 - 19:08
Dear volunteers,

All members of the SixTrack team would like to thank each of you for supporting our project at LHC@Home. The last weeks saw a significant increase in work load, and your constant help did not pause even during the Christmas holidays, which is something that we really appreciate!

As you know, we are interested in simulating the dynamics of the beam in ultra-relativistic storage rings, like the LHC. As in other fields of physics, the dynamics is complex, and it can be decomposed into a linear and a non-linear part. The former allows the expected performance of the machine to be at reach, whereas the latter might dramatically affect the stability of the circulating beam. While the former can be analysed with the computing power of a laptop, the latter requires BOINC, and hence you! In fact, we perform very large scans of parameter spaces to see how non-linearities affect the motion of beam particles in different regions of the beam phase space and for different values of key machine parameters. Our main observable is the dynamic aperture (DA), i.e. the boundary between stable, i.e. bounded, and unstable, i.e., unbounded, motion of particles.

The studies mainly target the LHC and its upgrade in luminosity, the so-called HL-LHC. Thanks to this new accelerator, by ~2035, the LHC will be able to deliver to experiments x10 more data than what is foreseen in the first 10/15y of operation of LHC in a comparable time. We are in full swing in designing the upgraded machine, and the present operation of the LHC is a unique occasion to benchmark our models and simulation results. The deep knowledge of the DA of the LHC is essential to properly tune the working point of the HL-LHC.

If you have crunched simulations named "workspace1_hl13_collision_scan_*" (Frederik), then you have helped us in mapping the effects of unavoidable magnetic errors expected from the new hardware of the HL-LHC on dynamic aperture, and identify the best working point of the machine and correction strategies. Tasks named like "w2_hllhc10_sqz700_Qinj_chr20_w2*" (Yuri) focus the attention onto the magnets responsible for squeezing the beams before colliding them; due to their prominent role, these magnets, very few in number, have such a big impact on the non-linear dynamics that the knobs controlling the linear part of the machine can offer relevant remedial strategies.

Many recent tasks are aimed at relating the beam lifetime to the dynamic aperture. The beam lifetime is a measured quantity that tells us how long the beams are going to stay in the machine, based on the current rate of losses. A theoretical model relating beam lifetime and dynamic aperture was developed; a large simulation campaign has started, to benchmark the model against plenty of measurements taken with the LHC in the past three years. One set of studies, named "w16_ats2017_b2_qp_0_ats2017_b2_QP_0_IOCT_0" (Pascal), considers as main source of non-linearities the unavoidable multipolar errors of the magnets, whereas tasks named as "LHC_2015*" (Javier) take into account the parasitic encounters nearby the collision points, i.e. the so called "long-range beam-beam effects".

One of our users (Ewen) is carrying out two studies thanks to your help. In 2017 DA was directly measured for the first time in the LHC at top energy, and nonlinear magnets on either side of ATLAS and CMS experiments were used to vary the DA. He wants to see how well the simulated DA compares to these measurements. The second study seeks to look systematically at how the time dependence of DA in simulation depends on the strength of linear transverse coupling, and the way it is generated in the machine. In fact, some previous simulations and measurements at injection energy have indicated that linear coupling between the horizontal and vertical planes can have a large impact on how the dynamic aperture evolves over time.

In all this, your help is fundamental, since you let us carry out the simulations and studies we are interested in, running the tasks we submit to BOINC. Hence, the warmest "thank you" to you all!
Happy crunching to everyone, and stay tuned!

Alessio and Massimo, for the LHC SixTrack team.
Kategórie: Novinky z projektov

LHC@home down-time due to system updates

LHC@home - Ut, 23.01.2018 - 11:19
Tomorrow Wednesday 24/1, the LHC@home servers will be unavailable for a short period while our storage backend is taken down for a system update.

Today, Tuesday 23/1, some of the Condor servers that handle CMS, LHCb and Theory tasks will be down for a while. Regarding the on-going issues with upload of files, please refer to this thread.

Thanks for your understanding and happy crunching!
Kategórie: Novinky z projektov
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